What is KB408 studying for alpha-1 antitrypsin deficiency?

KB408 is being studied as an inhaled gene therapy for alpha-1 antitrypsin deficiency. Researchers aim to evaluate its safety and how it affects important proteins related to the condition. This trial is sponsored by Krystal Biotech, Inc. to explore a new treatment approach for adults with this genetic lung disease.

Who may be eligible for this alpha-1 antitrypsin deficiency clinical trial?

Adults aged 18 to 70 years with a confirmed PI*ZZ or PI*ZNull genetic diagnosis may be eligible. Participants should be clinically stable, have adequate lung function, and agree to certain treatment pauses if receiving augmentation therapy. Both men and women can participate. Please review eligibility criteria for more details.

Is there any cost to participate in this alpha-1 antitrypsin deficiency clinical trial?

Study-related care, including the study drug and all trial visits, is provided at no cost. However, personal travel and other expenses may vary and are not guaranteed to be covered. Participants should plan accordingly for any costs outside of study procedures.

Actively Recruiting

Phase 1

Age: 18Years - 70Years

All Genders

ID06049082

Phase 1 Study of Inhaled KB408 Gene Therapy for Adults With Alpha-1 Antitrypsin Deficiency

Led by Krystal Biotech, Inc. · Updated on 2025-07-22

Participants Needed

Research Sites

52 weeks

Total Duration

AI-Summary

What this Trial Is About

Researchers are studying KB408, a specially designed inhaled gene therapy using a non-replicating herpes simplex virus vector to deliver functional human SERPINA1 gene to the lungs of adults with alpha-1 antitrypsin deficiency AATD. This trial targets adults aged 18 to 70 with specific genetic forms of AATD PI*ZZ or PI*ZNull to evaluate safety and how the treatment affects biological markers related to the disease. The study is a Phase 1 trial conducted by Krystal Biotech, Inc. to assess initial safety and pharmacodynamics of KB408. The study involves four groups three single-dose groups receiving low, mid, or high doses of nebulized KB408, and one group receiving multiple doses at the mid-level dose. Participants receiving intravenous augmentation therapy must pause this treatment for at least 10 days before and during the repeat dose and high-dose groups. The investigational drug, KB408, is administered via nebulization to deliver the gene therapy directly to the airways. Participants will be monitored closely for safety over 2 to 3 months, including tracking adverse events, vital signs, lung function tests, ECGs, and laboratory tests. Researchers will also measure levels of alpha-1 antitrypsin and neutrophil elastase in blood and lungs to understand the treatments biological effects. The study observes participants for changes from baseline to evaluate tolerability and pharmacodynamics of KB408 during and after dosing.

CONDITIONS

Brief Title

A Study of KB408 for the Treatment of Alpha-1 Antitrypsin Deficiency

Who Can Participate

Age: 18Years - 70Years

All Genders

Eligibility Criteria

You may qualify if you...

The subject or legally authorized representative must have read, understood, and signed an Institutional Review Board approved Informed Consent Form and be willing and able to follow study procedures.
Age between 18 and 70 years at the time of informed consent.
Genetically confirmed diagnosis of alpha-1 antitrypsin deficiency with a PIZZ or PIZNull genotype.
For Cohort 2b and Cohort 3: Willingness to wash out intravenous AAT augmentation therapy for at least 10 days before screening and to remain off it during the study.
For Cohort 2b and Cohort 3: Serum alpha-1 antitrypsin level below 11 micromolar at screening.
Willingness to remain on a stable treatment regimen during the study.
Resting oxygen saturation of 92% or higher on room air at screening.
Clinically stable and in good general health except for alpha-1 antitrypsin deficiency as determined by the investigator.

You will not qualify if you...

Forced expired volume in 1 second (FEV1) after bronchodilator less than 40% predicted at screening.
Diffusing capacity of lungs for carbon monoxide (DLCO) less than 30% predicted within 2 years prior to screening or at screening.
Known ongoing or history of significant lung problems other than alpha-1 antitrypsin deficiency.
Pulmonary exacerbation within 42 days before first dose.
Any new chronic therapy or change in ongoing therapy within 28 days before first dose.
Participation in another interventional study or investigational agent treatment within 30 days or 5 half-lives before first dose.
History of or listed for solid organ transplant or major lung surgery within 6 months before first dose.
Any condition or illness that may affect ability to complete study or pose additional safety risk.
Active oral herpes infection within 30 days before first dose.
Significant liver dysfunction including elevated liver enzymes or bilirubin or clinical signs of cirrhosis.
Smoking or use of tobacco, e-cigarettes, or recreational inhalants within 6 months before screening.
Unwillingness to abstain from smoking or related products throughout the study.
Positive urine cotinine test consistent with active smoking at screening, except when due to nicotine replacement therapy.
Abnormal blood counts or chemistry that may interfere with safety assessment.
Known noncompliance or unlikely to follow study protocol.
Pregnant or nursing females.
Unwillingness to follow contraception requirements per protocol.

Research Team

David Sweet, MD, PhD

Brittani Agostini, RN, CCRC

Not the Right Trial for You?

Explore thousands of other clinical trials that might be a better match.
Sign up to get personalized trial recommendations delivered to your inbox.

Already have an account? Log in here

Phase 1 Study of Inhaled KB408 Gene Therapy for Adults With Alpha-1 Antitrypsin Deficiency

On this page

AI-Summary

What this Trial Is About

Brief Title

Who Can Participate

Eligibility Criteria

Research Team

Not the Right Trial for You?

On this page

Who Can Participate

Eligibility Criteria